This project seeks to elucidate the functions in intact animals of specific extracellular matrix proteins and cell surface adhesion receptors. Particular attention will focus on fibronectin, its integrin receptors and the selectins. These proteins are thought to play important roles in development, including that of the heart and vascular system and in the interactions of circulating blood cells with the endothelial cells and basement membrane of the vessel wall. By generating mice with mutations in the genes encoding these adhesive proteins it will be possible to analyze their contributions to specific processes in vivo. The processes of most immediate interest to the overall aims of the Program of Excellence will be the focus of the research. These include development of the heart, cardiac defects, vasculogenesis, angiogenesis, hematopoiesis, lymphocyte and leukocyte traffic, various inflammatory responses including those involved in asthma and atherosclerosis as well as others.